Antirachitic preparations and process for making same



?atented Aug. 23 i932 ADOLF WINDAUS, F GOTTINGEN, GERMANY No Drawing. Application filed November 28, 1927, Serial No. 236,385, and in Germany January 14, 1927.

The present invention relates to a new compound having a high anti-rachitic eliicacy and to a process of preparing the same, and this application is a continuation in part of my copending application for Letters Patent of the United States for process for the manufacture of anti-rachitic preparations filed March 3, 1927, Serial No. 172,563. It is known that efficacy against rickets can be 0 imparted to cholesterine or phytosterine by.

exposing them to ultraviolet radiations.

According to this invention ergosterol, which is a high molecular crystallized alcohol containing several double bonds and deriving its name from its occurrence in ergot (Zeitschr. f. Physiolog. Chemie, 124C, 1923,

page 8) is converted whenexposed to the radiations of ultra-violet rays, into a. new compound having a high anti-r'achitic efficacy. 1

' My process is preferably carried out by subjecting a solution of ergosterol in alcohols, such as ethyl alcohol, in benzene, in

gasoline, in oils, or in similar solvents, to the as action of active rays as, for example, ultraviolet rays artificially produced by a mercury vapor lamp. The exposure to the rays may be effected in several ways. For exam ple, a good result is obtainable when dipping so the cooled ultra-violet lamp into the solution.

It is essential to exclude oxygen when carrying out the process, since the reaction product eagerly absorbs oxygen, especially when irradiated, thereby losing its anti-rachitic activity. Instead of exposing pure ergosterol to the radiations, extracts which contain enriched ergosterine for example yeast fat, can be employed with advantage.

In comparison with ergosterol my new; product is easily soluble in alcohol or oils. Its anti-rachitic efiicacy is extremely strong. My new product is superior in etlicacy to all hitherto known anti-raehitic agents, for instance, it is more than a thousand times as efficacious as cholesterine which has been exposed to ultra-violet radiations. For exam.- ple, an average daily dose for rachitic children is 2-4 mg, and even less. It is not precipitated by a solution of digitonin as 59 ergosterol. Furthermore, its spectrum of the ing material is yielded. Care has to be taken ultra-violet region is different from that of ergosterol. Its alcoholic solution shows in a polarized light a slight dextrorotation while the solutions of ergosterol have a levorotation. g The following example is intended to illustrate my invention, without, however, limit ing it thereto.

A solution of 100 g. ergosterol in liters of ethyl alcohol is subjected to the action of the ultra-violet rays of a quartz mercury vapor lamp which is dipped under cooling into the solution while conducting a continuous stream of nitrogen through the reaction vessel in order to exclude oxygen. The reaction is controlled by treating, from time to time,- a sample with a solution of 1% digitonin. The reaction is interrupted when not more than a small precipitate of the startthat the radiation is not continued too long, as otherwise the resulting vitamin can be destroyed.

The alcoholic solution is then evaporated in vacuo to about 1 liters, and cooled, whereby about 10% unchanged ergosterol crystallizes out, and after having filtered ofli' the starting material the solution is completely evaporated in vacuo. The use of a vacuum may be dispensed with.

The necessary daily healing dose for rickets of rats is 1/10,000 to 1/25,000 mg. and less,

usually given during the tim'e of about two to three weeks.

Claims:

1. The process which comprises dissolving previouslyisolated ergosterol, substantially free of materials which are normally associated with it in nature, in a chemically and photochemically inert organic 'ergosterol solvent, and exposing said solution to light having an activating action until a sample treated with a solutionof 1% digitonin yields only a small precipitate.

'2- The process which comprises dissolving previously isolated ergosterol, substantially free of materials which are normally associated withit in nature, in a chemically and photochemically inert aliphatic oxygencontaming organic ergosterol solvent, and ex- 1% product "obtained by subjecting ergosterol posing saidsolution to light having an acti-'- 'vating action until'a sample treated with a solution of 1 precipitate. 3. As a new yields only a small article of manufacture, the

substantial .free': of materials which are normall associated'witli it in nature toactivation y means .of ultra-violet light rays, said amt . .into the solution until a sample treated with product being a resinous oil distinguished by ing more soluble in alcohol-than'ergostero by showing in polarized light a slight dextrorotation, and by having a degree" of antirachitic eflicacy more than one thousand,

times thatof cholesterine which has been factivated byultra-violet light rays to its maximum anti rachitic eflicacy.

4. The process which comprises e os'ing a solution of ergosterol substantially. reeof materials which are normally associated with materials which are normally associated with .it in nature in ethyl alcohol to light having an activatin *action until a sample treated with a 5011111011 of 1% digitonin yields only a small precipitate. 4

5. The process which consists in sub ecting asolutlon of ergosterol substantially'free of materials' which are normally associated with it in nature in ethyl alcohol to the action of ultra-violet rays produced by a quartz mercury vaporlamp dipped under cooling a solution of-1':% di 'tonin yields only a small precipitate, strong alcoholic solution, separating the unchanged ergosterol by cooling the concentrated alco-. holic solution and evaporating the filtratecompletely.

6. The process which consists in subjecting I a solution of ergosterol substantially free of Vmaterials' which are normally associated -,with it in nature in ethyl alcohol, while exeluding oxygen, to the action of ultra-violet f rays produced by a quartz mercury vapor lamp dipped into the solution until a sample treated with a solution of 1% digitonin yields only a small precipitate, strongly evaporatmg then the valcoholic solution, separating the unchanged ergosterol by cooling the concentrated alcoholic solution and evaporating the filtrate completely. 7. he process which materials which are normally associated with consists in subjecting a solution of ergosterol substantially free of evaporating then the it in nature in ethyl alcohol to the action of cury vaporflamp dipped under, cooling into the solution until a sampletreatedrwith. a solution of 1% digitoninyields only a small ultra-violet rays produced by a quartz mer- -precipitate, strongly evaporating-"then the unchanged ergosterol "by cooling the concen alcoholic solution in a vacuo, separating the trated alcoholic solution and evaporating the" filtrate completelyin a vacuo. Y

Y 8. The process which consists in subjecting I asolution of ergosterol substantially free of v 

